A multilevel intervention to personalize and improve tobacco treatment in primary care

PROJECT SUMMARY/ABSTRACT
Current tobacco treatment is limited by physicians infrequently prescribing cessation medication (<20%),
patients infrequently using cessation medication (~33%), and limited medication effectiveness (<30%). A
multilevel intervention to personalize tobacco treatment, based on substantial data linking genetically informed
markers to treatment response, has the potential to address these critical gaps by addressing multiple targets
in the cascade of treatment success. First, precision treatment may increase treatment effectiveness by
matching the smoker with the medication that maximizes efficacy and safety. Second, it may increase
physicians’ likelihood of prescribing because they expect precision treatment to be more effective than
standard treatment. Third, precision medicine may increase patients’ motivation to initiate and adhere to
cessation medication, as evidence suggests that smokers express desire for gene-guided treatment and
increased motivation to use it adherently. Emerging evidence including a recent Cochrane review and our
research suggests that patients’ ability to quit smoking and respond to cessation medication are associated
with multiple biomarkers involved in nicotine metabolism (i.e., nicotine metabolite ratio, NMR) and nicotinic
receptor function (i.e., genotype of CHRNA5 variant rs16969968). Evaluating precision treatment based on
multiple markers in a multilevel intervention using behavior change theories will advance the field of tobacco
treatment. Our preliminary work demonstrated: 1) promise of using both genetic and metabolic markers in
guiding treatment, 2) high interest in gene-guided treatment and its potential for enhancing medication use
among smokers, 3) higher motivation for smoking cessation with use of genetic risk communication feedback
tools, and 4) successful use of health informatics to implement a multilevel tobacco intervention in clinic
settings. The proposed study aims to test a multilevel intervention precision treatment intervention using both
genetic and metabolic markers, directed at physicians and patients, to increase the uptake and effectiveness of
tobacco treatment in primary care. We propose a 2-arm cluster randomized controlled trial of 40 physicians
and 800 patients who smoke randomized to usual care (UC) vs. precision treatment (PT) based on NMR and
genetics in primary care. We hypothesize that PT will enhance cessation success via increased physician
prescription of medication, patient adherence, and treatment effectiveness. In Aims 1 and 2, we will test the
impact of PT on physician prescribing, patient use of medication, and patient smoking abstinence. In Aim 3, we
will evaluate mechanisms of behavior change and implementation outcomes. The study reflects a significant
and innovative paradigm shift from a traditional treatment model to precision treatment that includes both
metabolic and genetic markers to motivate and guide tobacco treatment for both physicians and patients,
integrated within primary care.

Grant Number: 5R01DA056050-04
NIH Institute/Center: NIH
Principal Investigator: Li-Shiun Chen